Bleeding and coagulation Flashcards
What is haemostasis?
The arrest of bleeding and maintenance of vascular patency
What is primary and secondary haemostasis?
Primary haemostasis is the formation of a platelet plug
Secondary haemostasis is the formation of a fibrin clot
Where are platelets formed?
Platelets are formed in the bone marrow by budding from megarokaryocytes
What is the life span of a platelet?
7-10 days
What are some of the possible causes of failure of platelet plug formation?
Vascular causes
E.g reduced collagen in blood vessels in elderly patients and inherited causes such as marfan’s
Thrombocytopenia due to anti-platelet medications and NSAIDs
Von Willebrand disease
Lack of vitamin C e.g scurvy
Which is generally more severe, failure of primary haemostasis or failure of secondary haemostasis?
Failure of secondary haemostasis
How does failure of platelet plug formation present?
Spontaneous bruising and purpura (usually in the lower limbs due to gravity)
Mucosal bleeding (epistaxis, GI, conjunctival and menorrhagia)
Intracerebral bleeds in severe cases
What is the screening test for primary haemostasis?
Platelet count
What are the screening tests for secondary haemostasis?
Prothrombin time
Activated partial thromboplastin time
What are some of the naturally occurring anticoagulants?
Anti-thrombin
Protein C and S
Does prothrombin time test the extrinsic or the intrinsic pathway?
Extrinsic pathway
It measures the propagation side of fibrin clot formation
What is the normal range for prothrombin time?
12-13 seconds
What are some of the causes of a prolonged PT?
Warfarin therapy
DIC
Liver disease
Vitamin K deficiency (premature babies and ITU patients)
Does the APTT test the extrinsic or the intrinsic pathway?
Intrinsic pathway
Measure the amplification side of fibrin clot formation
What is the normal range for APTT?
30-40 seconds
What are some of the possible causes of prolonged APTT?
Heparin therapy
Haemophilia
VW disease
Antiphospholipid syndrome
Thrombocytopenia is the most common cause of primary haemostatic failure. What are some of the possible cause of thrombocytopenia?
Cancer
DIC
Immune thrombocytopenic purpura
What is immune thrombocytopenic purpura?
An autoimmune cause of thrombocytopenia which involves antibodies against platelets
how is immune thrombocytopenic purpura managed?
Prednisolone (steroids)
VWF deficiency can be acquired or hereditary. Which is more common?
Mostly hereditary
What mode of inheritance does VWF disease involve?
Autosomal dominant
VWF affects men and women equally, so why are men less likely to be diagnosed?
Women are more likely to present as they may have the symptom of menorrhagia
The condition may not become apparent in men until they have an accident or operation and notice abnormal bleeding
Is haemophilia due to a single or multiple clotting factor deficiencies?
Single clotting factor deficiency
Where are coagulation factors synthesised?
In hepatocytes in the liver
What happens to coagulation factors in liver failure?
Coagulation factors are reduced
What are the four clotting factors?
II, VII, IX and X
2,7,9 and 10
Where is vitamin K absorbed?
What does it require for absorption?
Vitamin K is absorbed in the upper intestine
Requires bile salts for absorption
What are some of the possible causes of vitamin K deficiency?
Warfarin
Diet/ malabsorption
Obstructive jaundice (e.g pancreatic cancer)
Haemorrhagic disease of the newborn
Why does DIC occur?
All the clotting factors are used up in thrombus formation
What are some of the possible causes of DIC?
Sepsis
Obstetric emergencies
Malignancy
Hypovolaemic shock (hypoxia causes tissue damage)
How is DIC managed?
Treat the underlying cause (e.g antibiotics or removing the placenta)
Platelets and plasma transfusions and fibrinogen replacement
What mode of inheritance does haemophilia involve?
X-linked inheritance
only affects males
Where are the most common sited of bleeding in haemophilia?
Ankle, knee and elbow joints
These sites take a lot of strain and get a lot of bumps
Is haemophilia A or B more common?
Haemophilia A is most common
Which coagulation factor deficiencies do haemophilia A and B involve?
Haemophilia A - factor VIII deficiency
Haemophilia B - factor IX deficiency
What are some of the clinical features of haemophilia?
Recurrent haemarthroses (blood in the joint – very painful and limits movement
Recurrent soft tissue bleeds (e.g bruising in toddlers)
Tend to bleed into big muscles e.g iliopsoas
Prolonged bleeding after dental extractions, surgery and invasive procedures
How is haemophilia managed?
Infusions of factor VIII
Joint replacements
Which class of drugs are arterial Vs venous thrombotic events treated with?
Arterial - anti-platelets
Venous - anti-coagulants
Is venous thrombosis a problem of primary or secondary haemostasis?
Problem of secondary haemostasis - involves the formation of a fibrin clot
What are the components for Virchow’s Triad?
Stasis
vessel wall (valve problems)
Hypercoagulability
What is the strongest risk factor for venous thromboembolism?
Having had a previous DVT or PE
What is thrombophilia?
Familial or acquired disorders which predispose to thrombosis
Give some examples of hereditary thrombophilias
Factor V Leiden
Antithrombin deficiency
Protein C or S deficiency
What are the indications for screening for thrombophilia?
Venous thrombosis at <45 years old
Recurrent or unusual venous thrombosis
FH of venous thrombosis or thrombophilia
What are the components of antiphospholipid antibody syndrome?
Recurrent thromboses
Recurrent miscarriage
Mild thrombocytopenia
How is antiphospholipid syndrome managed?
Aspirin / Warfarin
(can get venous or arterial thrombosis)
*Heparin should be used in pregnancy
Is arterial thrombosis a problem of primary or secondary haemostasis?
Arterial thrombosis is a problem of primary haemostasis - involves the formation of a platelet rich thrombus
How do platelets bind to sub endothelial collagen?
platelet adhesion
Via glycoprotein 1b and VWF
How doe platelets attach to eachother?
platelet aggregation
Via GPIIbIIIa and fibrinogen
An isolated prolonged partial thromboplastin time selects a deficiency of factors in which pathway?
The intrinsic pathway
Factor VIII deficiency is a deficiency in which pathway?
The intrinsic pathway
An isolated prolonged prothrombin time reflects a deficiency of factors involved in which pathway?
The extrinsic pathway
Deficiencies in common pathway factors cause a prolongation of both the prothrombin time and the activated partial thromboplastin time. Which clotting factors are involved in the common pathway?
II, V and X
Factor VII deficiency is a deficiency in which pathway?
The extrinsic pathway